Brain-dead Organ Donors Research Articles

A survey of the nursing care for the families of brain-dead organ donors

A survey of the nursing care for the families of brain-dead organ donors

Never Declared Brain Dead Potential Organ Donors-An Additional Source of Donor Organs?

Patients never declared brain dead may represent an additional source of donor organs. To determine the number of likely brain dead potential donors who are never declared brain dead and to compare them with brain dead and donation after cardiac death potential organ donors. This study was a retrospective chart review of all catastrophically brain-injured patients referred to a single-organ procurement organization (OPO) over a 4-year period. This study identified 159 likely brain dead potential organ donors, 902 brain dead potential organ donors, and 357 potential donation after circulatory death donors over a 4-year period. None. This study did not predetermine outcome measures before data collection because the study group, likely brain dead potential organ donors, had not previously been described. Likely brain dead potential donors were significantly older than brain dead potential donors ( P < .0001) but were otherwise not different demographically. They were more likely to be a late referral to the OPO ( P < .0001) and less likely to be in the donor registry ( P < .0001). The most commonly identified factors associated with a failure to declare brain death were an unwillingness to continue supportive care by the family, premention of donation, a nontimely imminent death referral, known prior objection to donation, terminal instability, and a lack of cooperation with the OPO.

Presence of Human Herpesvirus 6B in the Pancreas of Subjects With and Without Type 1 Diabetes.

The aims of this study were to investigate the presence of human herpesvirus 6 (HHV6) A and B in human pancreata and to search for signs of active infection in this organ of subjects with and without type 1 diabetes (T1D). Pancreata from brain-dead organ donors with and without T1D were examined for the presence of HHV6 genomic sequences by polymerase chain reaction (PCR), transcripts by reverse transcriptase-PCR, and protein by immunohistochemistry. Quantitative PCR of isolated pancreatic islets and exocrine cell clusters was used to determine the intrapancreatic location of HHV6 DNA. Human herpesvirus 6B genomic sequences were present in 1 of 2 donors who died of acute-onset T1D, 4 of 6 donors with long-standing T1D, and 9 of 12 nondiabetic donors. Higher copy numbers of HHV6B DNA were present in isolated islets than in exocrine tissue from the same donors. No signs of active HHV6 transcription were found. Human herpesvirus 6A was not present in any tested pancreas. The herein presented data demonstrate, for the first time, the presence of a latent HHV6B infection in the pancreas and islets of Langerhans. Whether this virus can contribute to disease in the pancreas remains to be determined.

Quantifying the Effects of Different Neutral Proteases on Human Islet Integrity

Efficient islet release from the pancreas requires the combination of collagenase, neutral protease (cNP), or thermolysin (TL). Recently, it has been shown that clostripain (CP) may also contribute to efficient islet release from the human pancreas. The aim of this study was to evaluate the impact of these proteases on human islet integrity in a prospective approach. Islets were isolated from the pancreas of 10 brain-dead human organ donors. Purified islets were precultured for 3 to 4 d at 37 °C to ensure that preparations were cleared of predamaged islets, and only integral islets were subjected to 90 min of incubation at 37 °C in Hank’s balanced salt solution supplemented with cNP, TL, or CP. The protease concentrations were calculated for a pancreas of 100 g trimmed weight utilizing 120 dimethyl-casein units of cNP, 70,000 caseinase units of TL, or 200 benzoyl-l-arginine-ethyl-ester units of CP (1×). These activities were then increased both 5× and 10×. After subsequent 24-h culture in enzyme-free culture medium, treated islets were assessed and normalized to sham-treated controls. Compared with controls and CP, islet yield was significantly reduced by using the 5× activity of cNP and TL, inducing also fragmentation and DNA release. Viability significantly decreased not until adding the 1× activity of cNP, 5× activity of TL, or 10× activity of CP. Although mitochondrial function was significantly lowered by 1× cNP and 5× TL, CP did not affect mitochondria at any concentration. cNP- and TL-incubated islets significantly lost intracellular insulin already at 1× activity, while the 10× activity of CP had to be added to observe a similar effect. cNP and TL have a similar toxic potency regarding islet integrity. CP also induces adverse effects on islets, but the toxic threshold is generally higher. We hypothesize that CP can serve as supplementary protease to minimize cNP or TL activity for efficient pancreas digestion.

Effects of Polyethylene Glycol 20,000 on the Management of Brain Dead Organ Donors in a Canine Model

Wickramaratne, Niluka MD; Liebrecht, Loren MD; Reichstetter, Heather; Fyffe-Freil, Ria; Blocher, Charles; Aboutanos, Michel B. MD, MPH, FACS; Mangino, Martin PhD Author Information

Human immunology studies using organ donors: Impact of clinical variations on immune parameters in tissues and circulation.

Organ donors are sources of physiologically healthy organs and tissues for life-saving transplantation, and have been recently used for human immunology studies which are typically confined to the sampling of peripheral blood. Donors comprise a diverse population with different causes of death and clinical outcomes during hospitalization, and the effects of such variations on immune parameters in blood and tissues are not known. We present here a coordinate analysis of innate and adaptive immune components in blood, lymphoid (bone marrow, spleen, lymph nodes), and mucosal (lungs, intestines) sites from a population of brain-dead organ donors (2 months-93 years; n=291) across eight clinical parameters. Overall, the blood of donors exhibited similar monocyte and lymphocyte content and low serum levels of pro-inflammatory cytokines as healthy controls; however, donor blood had increased neutrophils and serum levels of IL-8, IL-6, and MCP-1 which varied with cause of death. In tissues, the frequency and composition of monocytes, neutrophils, B lymphocytes and T cell subsets in lymphoid or mucosal sites did not vary with clinical state, and was similar in donors independent of the extent of clinical complications. Our results reveal that organ donors maintain tissue homeostasis, and are a valuable resource for fundamental studies in human immunology.

Understanding the effect of corticosteroid pretreatment in brain-dead organ donors: new mechanistic insights for improvement of organ quality in liver transplantation.

Transplant surgeons are currently faced with the challenge to accept marginal liver transplants due to steatosis or old age. Improving organ quality by implementing a selective organ protective donor management could be the first step towards a graft of enhanced quality. However, the molecular mechanisms of such treatments are still poorly understood. Glucocorticoid medication in donor medicine has been carried out and discussed for a long time. In a recent study published in Clinical Science, Jiménez-Castro et al. [Clin. Sci. (2017) 131, 733-746] demonstrate how liver histology and transplant liver function can be improved by administration of glucocorticoids to brain-dead donor rats with steatotic livers. This work illustrates the need for further trials in order to selectively improve the quality of steatotic livers with a potential for liver transplantation.

Honoring Donor Designation in Brain Dead Organ Donors

Honoring Donor Designation in Brain Dead Organ Donors

Physiologic Features of Brain Death.

Brain death is known to be associated with physiologic derangements but their incidence is poorly described. Knowledge of the changes that occur during brain death is important for management of the potential organ donor. Thus, we sought to characterize the pathophysiology that occurs during brain death in patients with traumatic injuries. All brain-dead patients over a 10-year period were identified from the trauma registry at a level 1 urban trauma center. Patient demographics, injury characteristics, and clinical data for defining organ dysfunction were reviewed for the 24 hours surrounding brain-death declaration. Three hundred and seventy-three patients were identified. Mean age was 37 years (±17.2). Seventy-five per cent were male. Major mechanism of injury was blunt trauma in 66 per cent. Median injury severity score was 34 (IQR 25-43) with a median head abbreviated injury scale score of 5. The most common physiological disturbance was hypotension with 91 per cent of subjects requiring vasopressors. Thrombocytopenia and acidosis both had an incidence of 79 per cent. The next most common disturbances were hypothermia and moderate-to-severe respiratory dysfunction in 62 per cent. Myocardial injury was seen in 91 per cent but only 5.7 per cent of patients manifested severe cardiac dysfunction with an ejection fraction of <35. Diabetes insipidus was diagnosed in 50 per cent of patients. Interestingly, coagulopathy was noted in only 61.3 per cent, and hyperglycemia was seen in 36 per cent despite widespread belief that these occur universally during brain death. This is the first and largest study to characterize the incidence of pathophysiological disturbances following brain death in humans. Appropriate management of these dysfunctions is important for support of potential brain-dead organ donors.

Lack of Impact of Hyperchloremia in Brain-Dead Organ Donors on the Onset of Kidney Allograft Function in the Recipients

BackgroundHyperchloremia produces renal vasoconstriction and fall in glomerular filtration rate. In 90% of brain-dead organ donors, diabetes insipidus develops, characterized by inappropriate diuresis, hyperosmolality, and hyperchloremia. The aim of this study was to determine the relationship between the serum concentration of chlorides of the donor and the onset of the function of the kidney allograft in the recipient. MethodsWe retrospectively studied 213 donors and kidney allograft recipients. Serum creatinine concentrations and glomerular filtration rates on the 1st, 7th, and 30th days after transplantation of the recipients from hyperchloremic donors were compared with the recipients from normochloremic donors, as well as the incidences of acute tubular necrosis and delayed graft function. ResultsOn the 1st day, serum creatinine concentrations of the recipients from hyperchloremic and normochloremic donors, respectively, were 448.2 ± 212.1 μmol/L and 502.2 ± 197.8 μmol/L (P = .1), on the 7th day, 168.6 ± 102.6 μmol/L and 196.9 ± 120.6 μmol/L (P = .13), and on the 30th day, 129.4 ± 43.3 μmol/L and 131.8 ± 43.6 μmol/L (P = .73). The differences were statistically significant. The groups also did not differ significantly in glomerular filtration rates and incidences of acute tubular necrosis and delayed graft function. ConclusionsIn this study, no significant correlation between serum chloride concentrations of the organ donors and the onset of the function of kidney allografts in the recipients was found.

Determination of HLA-A, -B and -DRB1 polymorphism in brain dead organ donors representative of the Colombian general population, 2007-2014

Genes encoding for human leukocyte antigens (HLA) are highly polymorphic and of great importance in organ transplantation procedures, as determining allelic frequencies in defined populations is taken into account among the scientific criteria for organ allocation. The objective of this study was to establish the antigen HLA-A, -B, and -DRB1 haplotype frequencies in organ donors representative of the Colombian population after brain death. We conducted a descriptive retrospective study involving 2,506 cadaveric organ donors including an allelic and haplotype analysis of HLA-A, -B and -DRB1; we also determined the Hardy-Weinberg equilibrium. We identified 21, 43 and 15 allelic loci for groups A*, B* and DRB1*, respectively. We detected 1,268 HLA-A, -B and -DR, 409 HLA-A-B, 383 HLA-DR-B, and 218 HLA-A-DR haplotypes. The three loci were found to be in Hardy-Weinberg equilibrium between the number of heterozygotes observed and the expected number, with p values of ;0.05. This study provides information on the allelic distribution of HLA class I and II in organ donors from the six regions in which Colombia is structurally divided to provide transplant services.

Innate inflammatory gene expression profiling in potential brain-dead donors: detailed investigation of the effect of common corticosteroid therapy.

Our study aimed to assess the influence of common methylprednisolone therapy on innate inflammatory factors in potential brain-dead organ donors (BDDs). The study groups consisted of 50 potential BDDs who received 15 mg/kg/d methylprednisolone and 25 live organ donors (LDs) as control group. Innate immunity gene expression profiling was performed by RT-PCR array. Soluble serum cytokines and chemokines, complement components, heat shock protein 70 (HSP70) and high mobility group box-1 (HMGB1) were measured by ELISA. Surface expression of TLR2 and TLR4 were determined using flow cytometry. Gene expression profiling revealed up-regulation of TLRs 1, 2, 4, 5, 6, 7 and 8, MYD88, NF-κB, NF-κB1A, IRAK1, STAT3, JAK2, TNF-α, IL-1β, CD86 and CD14 in the BDD group. Remarkably, the serum levels of C-reactive protein and HSP70 were considerably higher in the BDD group. In addition, serum amounts of IL-1β, IL-6, TNF-α, HMGB1, HSP70, C3a and C5a, but not IL-8, sCD86 or monocyte chemoattractant protein-1, were significantly increased in the BDD group. Significant differences were observed in flow cytometry analysis of TLR2 and TLR4 between the two groups. In summary, common methylprednisolone therapy in BDDs did not adequately reduce systemic inflammation, which could be due to inadequate doses or inefficient impact on other inflammatory-inducing pathways, for example oxidative stress or production of damage-associated molecules.

Ex Situ Perfusion of Human Limb Allografts for 24 Hours.

Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion. Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL. Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury. Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.

Time trends in organ donation after neurologic determination of death: a cohort study.

The cause of brain injury may influence the number of organs that can be procured and transplanted with donation following neurologic determination of death. We investigated whether the distribution of causes responsible for neurologic death has changed over time and, if so, whether this has had an impact on organ quality, transplantation rates and recipient outcomes. We performed a cohort study involving consecutive brain-dead organ donors in southern Alberta between 2003 and 2014. For each donor, we determined last available measures of organ injury and number of organs transplanted, and compared these variables for various causes of neurologic death. We compared trends to national Canadian data for 2000-2013 (2000-2011 for Quebec). There were 226 brain-dead organ donors over the study period, of whom 100 (44.2%) had anoxic brain injury, 63 (27.9%) had stroke, and 51 (22.6%) had traumatic brain injury. The relative proportion of donors with traumatic brain injury decreased over time (> 30% in 2003-2005 v. 6%-23% in 2012-2014) (p = 0.004), whereas that with anoxic brain injury increased (14%-37% v. 46%-80%, respectively) (p < 0.001). Nationally, the annual number of brain-dead donors with traumatic brain injury decreased from 4.4 to less than 3 per million population between 2000 and 2013, and that with anoxic brain injury increased from 1.1 to 3.1 per million. Donors with anoxic brain injury had higher concentrations of creatinine, alanine aminotransferase and troponin T, and lower PaO2/FIO2 and urine output than donors with other diagnoses. The average number of organs transplanted per donor was 3.6 with anoxic brain injury versus 4.5 with traumatic brain injury or stroke (p = 0.002). Anoxic brain injury has become a leading cause of organ donation after neurologic determination of death in Canada. Organs from donors with anoxic brain injury have a greater degree of injury, and fewer are transplanted. These findings have implications for availability of organs for transplantation in patients with end-stage organ failure.

Diaphragm Abnormalities in Patients with End-Stage Heart Failure: NADPH Oxidase Upregulation and Protein Oxidation.

Patients with heart failure (HF) have diaphragm abnormalities that contribute to disease morbidity and mortality. Studies in animals suggest that reactive oxygen species (ROS) cause diaphragm abnormalities in HF. However, the effects of HF on ROS sources, antioxidant enzymes, and protein oxidation in the diaphragm of humans is unknown. NAD(P)H oxidase, especially the Nox2 isoform, is an important source of ROS in the diaphragm. Our main hypothesis was that diaphragm from patients with HF have heightened Nox2 expression and p47phox phosphorylation (marker of enzyme activation) that is associated with elevated protein oxidation. We collected diaphragm biopsies from patients with HF and brain-dead organ donors (controls). Diaphragm mRNA levels of Nox2 subunits were increased 2.5–4.6-fold over controls (p < 0.05). Patients also had increased protein levels of Nox2 subunits (p47phox, p22phox, and p67phox) and total p47phox phosphorylation, while phospho-to-total p47phox levels were unchanged. The antioxidant enzyme catalase was increased in patients, whereas glutathione peroxidase and superoxide dismutases were unchanged. Among markers of protein oxidation, carbonyls were increased by ~40% (p < 0.05) and 4-hydroxynonenal and 3-nitrotyrosines were unchanged in patients with HF. Overall, our findings suggest that Nox2 is an important source of ROS in the diaphragm of patients with HF and increases in levels of antioxidant enzymes are not sufficient to maintain normal redox homeostasis. The net outcome is elevated diaphragm protein oxidation that has been shown to cause weakness in animals.

Imaging of the Lungs in Organ Donors and its Clinical Relevance: A Retrospective Analysis.

The aim of the study was to retrospectively evaluate the diagnostic imaging that potential lung donors undergo, the reader variability of image interpretation and its relevance for donation, and the potential information gained from imaging studies not primarily intended for lung evaluation but partially including them. Bedside chest radiography and computed tomography (CT), completely or incompletely including the lungs, of 110 brain-dead potential organ donors in a single institution during 2007 to 2014 were reviewed from a donation perspective. Two chest radiologists in consensus analyzed catheters and cardiovascular, parenchymal, and pleural findings. Clinical reports and study review were compared for substantial differences in findings that could have led to a treatment change, triggered additional examinations such as bronchoscopy, or were considered important for donation. Among 136 bedside chest radiographs, no differences between clinical reports and study reviews were found in 37 (27%), minor differences were found in 28 (21%), and substantial differences were found in 71 (52%) examinations (P<0.0001). In 31 of 42 (74%) complete or incomplete CT examinations, 50 of 74 findings with relevance for lung donation were not primarily reported (P<0.0001). The majority of donor patients undergo only chest radiography. A targeted imaging review of abnormalities affecting the decision to use donor lungs may be useful in the preoperative stage. With a targeted list, substantial changes were made from initial clinical interpretations. CT can provide valuable information on donor lung pathology, even if the lungs are only partially imaged.

Complement-mediated inflammation and injury in brain dead organ donors.

The importance of the complement system in renal ischemia-reperfusion injury and acute rejection is widely recognized, however its contribution to the pathogenesis of tissue damage in the donor remains underexposed. Brain-dead (BD) organ donors are still the primary source of organs for transplantation. Brain death is characterized by hemodynamic changes, hormonal dysregulation, and immunological activation. Recently, the complement system has been shown to be involved. In BD organ donors, complement is activated systemically and locally and is an important mediator of inflammation and graft injury. Furthermore, complement activation can be used as a clinical marker for the prediction of graft function after transplantation. Experimental models of BD have shown that inhibition of the complement cascade is a successful method to reduce inflammation and injury of donor grafts, thereby improving graft function and survival after transplantation. Consequently, complement-targeted therapeutics in BD organ donors form a new opportunity to improve organ quality for transplantation. Future studies should further elucidate the mechanism responsible for complement activation in BD organ donors.

Intrapulmonary Percussive Ventilation as a Lung Recruitment Strategy in Brain-Dead Organ Donors.

To determine the strength of the evidence evaluating the effectiveness of intrapulmonary percussive ventilation (IPV) as a safe alternative or adjunctive therapy to traditional chest physiotherapy (CPT) among potential organ donors. Literature search conducted from February 2015 to November 2015 using PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, and bibliographies of pertinent articles. Search Terms: Intrapulmonary percussive ventilation, chest physiotherapy, chest wall oscillation, organ donors, and ventilation. Articles in English from 1994 to present directly compared IPV to CPT or conventional (no) therapy. Association of Critical-Care Nurses Levels of Evidence was used to determine the strength of evidence. Level B and level C articles were reviewed. No studies were found using IPV in the donor population. Results from studies using IPV in other populations indicated IPV had no adverse effects, improved sputum clearance and oxygenation, and reduced atelectasis and pneumonia in patients with artificial airways. Intrapulmonary percussive ventilation may be a safe and effective alternative or adjunctive to CPT therapy and improve the number of lungs available for transplantation. Clinical research is essential to determine the effectiveness of this therapy for lung recruitment in the donor population.

Correlation of Knowledge and Attitude in Blood Donation and Organ Donation

Objectives: To examine the knowledge and attitude of nursing students toward blood and organ donation, and to study the influence of knowledge toward the blood and organ donation attitude and will to practice. Methods/Statistical Analysis: It is a descriptive correlation study. The collected data is analyzed using SPSSWIN 18.0. Blood and organ donation knowledge and attitude of subject were analyzed using t-test, ANOVA and Bonferroni post examination. The relationship between knowledge and attitude of blood and organ donation was calculated using Pearson correlation coefficients, and the influential factor toward brain dead organ donation attitude used multi regression analysis. Findings: The blood donation knowledge score of subject ranged between 6 to 13, average of 10.25(SD=1.75), blood donation attitude score was between 48 to 88, average of 67.17(SD=9.35). The brain dead organ donation knowledge score was between 0 and 11, average of 4.66(SD=2.50), and the brain dead organ donor attitude score was between 41-70, average of 51.82(SD= 5.83). Blood donation knowledge showed difference in blood type (F=2.74, p=.046), and blood donation experience(t=-2.13, p=.035) and the blood donation attitude showed difference in religion (t=-2.24, p=.027), future blood donation plan(t=-2.93, p=.004), chronic disease in family tree(t=2.02, p=.045) and to whom one wants to donate the organ(F=-2.68, p=.008). The brain dead organ donation knowledge had no significant variables, and the brain dead organ donation attitude had showed difference in future blood donation plan (t=-4.40, p<.001), desire for brain dead organ donation (F=14.29, p<.001), organ donation communication (t=-5.65, p<.001), intention to organ donation (t=-3.20, p=.002). As for the brain dead organ donation attitude, it had significant qualitative correlation to blood donation attitude (r=.24 p=.009). Improvements/ Applications: Therefore, to create positive social consensus and promote necessity of blood and organ donation, there is a need for specific promotion regarding the knowledge through mass media to the public.

Influence of antithymocyte globulin treatment of brain-dead organ donor on inflammatory response in cardiac grafts: an experimental study in mice.

The expression of proinflammatory cytokines in donor hearts after antithymocyte globulin (ATG) treatment given prior to organ removal was evaluated to analyze changes in inflammatory response. Adult female OF-1 mice were randomized into brain death (BD) groups (BD Control, BD ATG) with or without treatment, and Controls (Control, ATG). BD induction was performed through gradual inflation of an intracranial positioned balloon catheter. At the end of a 6-h observation period, ATG (1mg/kg BW) was given intravenously. After 45min, the donor hearts were removed. Proinflammatory markers IL-2 and IL-6 were examined using ELISA and immunohistochemistry staining. After single administration of ATG, the inflammatory reaction in the myocardium showed a significant reduction in IL-2 expression (BD Control vs. BD ATG, P=0.033). Our investigation showed expected increase in proinflammatory mediators after BD. This increase was abolished by single infusion of ATG, indicated by significant reduction in IL-2 levels in the myocardium. We observed a reduction of IL-6 deposition in media cells in ATG-treated specimens. Further research is necessary to evaluate the role of ATG in donor management considering a potentially positive effect of ATG on IL-2-directed inflammatory response and possible reduction of IL-6-mediated vascular changes.